A novel approach for quantifying therapeutic monoclonal antibodies in blood through liquid chromatography-tandem mass...

Therapeutic monoclonal antibodies (mAbs) are increasingly used in clinical practice, but treatment efficacy varies, and high costs remain a concern. Therapeutic drug monitoring (TDM) with personalized dose adjustment can optimize outcomes. Volumetric absorptive microsampling (VAMS) offers a convenient, fixed-volume blood collection method that enables easy at-home sampling. However, its feasibility for TDM of mAbs has not been fully explored. This study aimed to develop and optimize an analytical method for quantifying trastuzumab, bevacizumab, and pembrolizumab in VAMS samples.

A 10-min extraction process efficiently recovered mAbs from VAMS, achieving extraction rates above 82.3 %. Ethylenediaminetetraacetic acid (EDTA) did not interfere with trypsin digestion, preventing quantification bias when using whole blood calibration curve. The method was validated according to international recommendations, demonstrating LOD ranges from 2 to 5 μg mL^-1 and LOQ ranges from 10 to 13.2 μg mL^-1. Accuracy ranged from 97.8 % to 115.3 %, with intraday and interday precisions (RSD) below 7.4 %. Moreover, the three mAbs remained stable in VAMS at room temperature for 30 days. A strong correlation was observed between mAb concentration in plasma and VAMS, confirming the method's reliability. Ultimately, the method was applied to cancer patients receiving these therapies. The determined concentrations were all within the expected therapeutic ranges, further supporting the method's clinical relevance.

The validated method simplifies the measurement of mAb concentration, reducing the need for invasive blood draws while ensuring accuracy and precision. Its strong correlation with plasma concentrations highlights its potential for TDM, enhancing personalized medicine and improving treatment outcomes for patients receiving mAb therapies.